The Administrative Core will provide organizational and scientific leadership for the program project. The DPG brings together a group of individuals with widely diverse talents and technical expertise (i.e., cell and molecular biology, morphology, pathology, biochemistry, etc.) to focus on the spatial and temporal regulation of angiogenesis. The overriding hypothesis for the PPG is that the tumor vasculature and other elements of tumor stroma are attractive therapeutic targets. To explore this hypothesis, the Principal investigator has worked with the project and core leaders to develop six central themes: i. Exploration of novel signaling pathways or molecules in angiogenesis. ii. Investigation of signaling pathways that intersect with the TR3/Nur77, PI3K/Akt, estrogen-estrogen receptor, and thrombospondin-1 pathways, iii. Mobilization and trafficking of bone marrow cells and their accumulation in tumor stroma. iv. Understanding the ultrastructural components and the molecular mechanisms that regulate vascular permeability, v. Investigations into the molecular basis of therapeutics in development of cancer, vi. Combinatorial therapeutic approaches to improve tumortherapy. The Administrative Core will manage the financial resources, facilitate communication between participants and make decisions regarding the scientific direction of the project. Drs. Dvorak and Lawler will make the final decisions regarding the allocation of resources and funds, the progress of the individual projects and the operation of the cores. They will address all issues that arise regarding changes in the various investigators' efforts or institutional affiliation. The opinions of the Executive Committee, the External Advisory Board and the Clinical Advisory Board will be carefully weighed in making these decisions. Facilitation of communication among the projects and core leaders is a key mission of the Administrative Core. It will organize, coordinate and document scientific and administrative meetings of the participants. These will include monthly meetings of the project leaders, core leaders, and postdoctoral and technical personnel who are involved in the project. These meetings will include a period of time for informal interactions, a presentation by an individual involved in one of the projects and a discussion period. The Administrative Core will also organize retreats (every 12 to 18 months) that will include the External Advisory Board and the Clinical Advisory Boards. The Administrative Core is developing a web site that will further enhance, communication n.y posting, information; regarding, internal and external meetings^ seminars, and data, as: weir as- arrTcfeas^section where anyorTefrrtrte-PFGcarrpasfa^qaestfanrarrraver'rTypxitrtesrEr.